Search Results (622)

Topical drug administration is a common method of delivering medications to the eye to treat various ocular conditions, including glaucoma, dry eye, and inflammation. Drug efficacy following topical administration, including the drug’s distribution within the eye, absorption and elimination rates, and physiological responses can be predicted using physiologically based pharmacokinetic (PBPK) modeling. High-resolution computational models of the eye are desirable to improve simulations of drug delivery; however, these approaches can have long run times. In this study, a fast-running computational quasi-3D (Q3D) model of the human tear film was developed to account for absorption, blinking, drainage, and evaporation. Visualization of blinking mechanics and flow distributions throughout the tear film were enabled using this Q3D approach. Average drug absorption throughout the tear film subregions was quantified using a high-resolution compartment model based on a system of ordinary differential equations (ODEs). Simulations were validated by comparing them with experimental data from topical administration of 0.1% dexamethasone suspension in the tear film (R² = 0.76, RMSE = 8.7, AARD = 28.8%). Overall, the Q3D tear film model accounts for critical mechanistic factors (e.g., blinking and drainage) not previously included in fast-running models. Further, this work demonstrated methods toward improved computational efficiency, where central processing unit (CPU) time was decreased while maintaining accuracy. Building upon this work, this Q3D approach applied to the tear film will allow for more seamless integration into full-body models, which will be an extremely valuable tool in the development of treatments for ocular conditions. Full article

Objective: To investigate the neuroprotective effects of a Rho-associated kinase (ROCK) inhibitor on retinal ganglion cells (RGCs) in vitro and in vivo. Methods: For in vivo studies, a unilateral optic nerve crush mouse model was established. Then, 100 mM Y-27632 (a ROCK inhibitor) or saline was applied to the experimental eyes once a day for 14 days. The effects of the ROCK inhibitor were evaluated by counting the surviving RGCs in the enucleated flat retina tissues and measuring the inner retinal thickness using optical coherence tomography (OCT), the amplitude of the electroretinogram (ERG), and the change in intraocular pressure (IOP). For the in vitro study, RGCs were isolated from five-day-old mice using a modified immunopanning method with magnetic beads. The isolated RGCs were incubated for 72 h with various concentrations of Y-27632, after which TUNEL assays were performed to determine the number of surviving RGCs. Results: Y-27632 has neuroprotective effects, as it significantly increased the number of surviving RGCs by approximately 6.3%. OCT and ERG data also revealed that Y-27632 induced neuroprotective effects in vivo; furthermore, Y-27632 reduced IOP by approximately 18.3%. The in vitro study revealed the dose-dependent neuroprotective effects of Y-27632, with the highest dose of Y-27632 (1000 nM) increasing the RGC survival rate after 72 h of incubation compared with that of the control. Conclusions: The ROCK inhibitor Y-27632 may exert some neuroprotective effects on RGCs when it is used as an eye drop through an IOP-independent mechanism. Full article

Objective: This study aimed to explore the acute neurophysiological effects of a single oral dose of Astragaloside IV (AS-IV) on EEG-measured brain oscillations and cognitive-relevant spectral markers in healthy young adults. Methods: Twenty healthy adults (8 females, 12 males; mean age: $23.4\pm 2.1$) underwent eyes-closed resting-state EEG recordings before and approximately 90 min after oral intake of 150 mg AS-IV. EEG data were collected using a 21-channel 10–20 system and cleaned via Artifact Subspace Reconstruction and Independent Component Analysis. Data quality was confirmed using a signal-to-noise ratio and 1/f spectral slope. Absolute and relative power values, band ratios, and frontal alpha asymmetry were computed. Statistical comparisons were made using paired t-tests or Wilcoxon signed-rank tests. Results: Absolute power decreased in delta, theta, beta, and gamma bands (p < 0.05) but remained stable for alpha. Relative alpha power increased significantly (p = 0.002), with rises in relative beta, theta, and delta and a drop in relative gamma (p = 0.003). Alpha/beta and theta/beta ratios increased, while delta/alpha decreased. Frontal alpha asymmetry was unchanged. Sex differences were examined in all measures that showed significant changes; however, no sex-dependent effects were found. Conclusions: A single AS-IV dose may acutely modulate brain oscillations, supporting its potential neuroactive properties. Larger placebo-controlled trials, including concurrent psychometric assessments, are needed to verify and contextualize these findings. A single AS-IV dose may acutely modulate brain oscillations, supporting its potential neuroactive properties. Full article

Background/Objectives: To evaluate the effectiveness and limitations of a newly developed unit-dose eye drop instillation aid in patients with glaucoma. Methods: Hospitalized adult glaucoma patients at the University of Yamanashi were enrolled if they had self-administered glaucoma eye drops for at least six months, had no upper limb impairments or cognitive decline, and had corrected visual acuity of ≥20/200 in at least one eye. This study used 0.1% hyaluronic acid mini-ophthalmic drops. Eye drop instillation was performed in the following order: without aid in the sitting position, with aid in the sitting position, without aid in the supine position, and with aid in the supine position. One practice trial with the device was conducted beforehand. Successful instillation was defined as delivery of a drop into the conjunctival sac without contact with the ocular surface, eyelashes, or face. Patients were also surveyed regarding the perceived usefulness of the device. Results: Sixty-three patients (37 males, 26 females; mean age 71.3 ± 11.2 years) participated. In the sitting position, the success rate improved significantly from 70.3% without the aid to 89.1% with the aid (p = 0.0005). Success rates decreased with age but improved more markedly in older patients. In the supine position, the rate was 76.6% without the aid and 100% with the aid (p < 0.0001). Conclusions: Unit-dose eye drop aids significantly increase the success rate of instillation, especially among elderly patients, and may contribute to better adherence and treatment outcomes in glaucoma care. Full article

Trabeculectomy with mitomycin C is a key surgical intervention for managing glaucoma when conservative treatments fail. The success of trabeculectomy is influenced by various factors, including preoperative ocular characteristics like conjunctival vascularity. This study aims to explore the relationship between the preoperative conjunctival vascular area and post-trabeculectomy outcomes in glaucoma patients. By analyzing the conjunctival vascular density, intraocular pressure (IOP), bleb morphology, laser suture lysis (LSL) frequency, and postoperative eye drops, this research sheds light on the impact of preoperative vascularity on surgical success. Results show that lower preoperative conjunctival vessel density is associated with favorable outcomes, such as better bleb formation and reduced need for postoperative interventions, while higher conjunctival vessel density correlates with complications like hyphema. These findings emphasize the importance of assessing preoperative conjunctival vascularity to optimize trabeculectomy outcomes and personalize treatment strategies for glaucoma patients. Full article

Objectives: Insulin plays a crucial role in neuronal survival and oxidative stress modulation, making it a potential therapeutic target. This study investigates the effects of insulin in combination with a mesenchymal cell-derived secretome in patients with degenerative neuroretinal diseases. Methods: Sixty-four patients with severe neuroretinal diseases who had previously undergone the Limoli Retinal Restoration Technique (LRRT) were included in this longitudinal study and divided into groups: group 1 received a single injection of 5 units of insulin lispro into the suprachoroidal space of the worse-seeing eye; group 2 received insulin injection in the better-seeing eye. Retinal function was assessed using microperimetry (MY) before and after treatment (approximately 1 year for eye drops). Group 3 consisted of patients who demonstrated improvement in MY after insulin injection. These patients continued treatment with daily insulin eye drops. Results: In group 1, insulin-treated eyes showed a significant increase in retinal sensitivity from 10.09 dB to 10.75 dB (p = 0.0067), while untreated eyes declined from 12.35 dB to 11.92 dB (p = 0.0448). In group 2, insulin-treated eyes improved from 10.8 dB to 11.63 dB (p = 0.05), whereas untreated eyes exhibited a decline from 8.68 dB to 8.50 dB (p = 0.6771). In group 3, patients using insulin eye drops showed a stabilization or mild increase in retinal sensitivity, from 11.39 dB to 11.73 dB (p = 0.231). Conclusions: The addition of insulin in patients previously treated with the LRRT was associated with improved sensitivity and a stabilizing effect on neuroretinal function. Full article

Dry eye disease (DED) is a hallmark of primary Sjögren’s disease (SjD) and often resists conventional treatments like lubricant eye drops. Insulin nanoemulsions offer a potential solution by improving drug penetration and retention on the ocular surface. In animal models, insulin has shown benefits in promoting tear secretion and corneal healing. This study evaluated the safety and efficacy of insulin nanoemulsion eye drops (20 IU/mL, three times daily for 30 days) in patients with SjD. Thirty-two patients were randomized in a double-masked design to receive either insulin or placebo drops. Symptoms (assessed by OSDI questionnaire) and objective measures (tear film breakup time, corneal and conjunctival staining, and Schirmer Test) were recorded at baseline, after 4 weeks of treatment, and at a 4-week follow-up. Twenty-three participants completed the study. Both groups showed significant improvement in symptoms and objective signs after treatment (p < 0.05), but no significant differences were found between the insulin and placebo groups. No clinically relevant adverse effects were reported. Insulin nanoemulsion eye drops are safe for SjD patients, but their therapeutic advantage remains unclear. Further studies with larger samples, extended follow-up, and dose adjustments are needed to better understand their potential. Full article

This review explores the potential role of topical insulin drops in corneal regeneration by analyzing the mechanism of action and clinical outcomes. Corneal integrity restoration is crucial for ocular surface healing. This review synthesizes the current literature on topical insulin for neurotrophic keratopathy (NK), highlighting its mechanism of action, therapeutic potential, and clinical outcomes. Recent studies report high rates of epithelial regeneration, suggesting that topical insulin may be an effective adjunct or alternative to conventional treatments. Further randomized controlled trials are needed to confirm its long-term efficacy and optimal dosing. Methods: Considering the limited regenerative capacity of the corneal epithelium in NK and the increasing interest in novel therapy, we review the existing literature to evaluate the role and extent of topical insulin’s contribution to corneal healing by applying the PICO framework, which allows for a clear and systematic approach to literature selection and evaluation. The literature search and study selection were conducted manually following PRISMA guidelines. Conclusions: Most of the studies resulting from the selection have small samples, and there is a lack of large, randomized clinical trials. The evidence reviewed in this study suggests that topical insulin is a promising therapy for promoting corneal healing in neurotrophic keratopathy. While clinical trials have demonstrated significant epithelial regeneration, optimal dosing and long-term safety require further investigation. Compared to conventional treatments such as autologous serum or growth factor therapy, insulin eye drops provide a cost-effective alternative. Additional research through controlled trials is needed to formulate standardized therapeutic protocols and verify long-term outcomes. Full article

Background/Objectives: To evaluate the efficacy and safety of using the preservative-free topical proxymetacaine hydrochloride (Minims, 0.5% w/v, Bausch & Lomb, UK) to control postoperative pain after epithelium-off corneal crosslinking (CXL) for keratoconus. Methods: This is an observational study of patients with mild to severe keratoconus who have undergone epithelium-off CXL. CXL was completed by applying dextran-free riboflavin (0.1%) for 10 min (Vibex Rapid; Avedro, Inc.), followed by continuous UV-A light (Avedro KXL system; Avedro, Inc.) for 30 min at an intensity of 3 mW/cm² and an energy of 5.4 J/cm². All patients were prescribed postoperative proxymetacaine hydrochloride PRN with an allowed frequency of up to eight times per 24 h for the first 3 days to control postoperative pain. Patients were reviewed at 1–2 weeks postoperatively for a comprehensive examination, including assessment of delayed corneal healing, removal of the bandage contact lens, and recording of subjective symptoms. Results: There were 223 eyes of 180 patients with a mean age of 24.9 ± 8.6 years (range: 13–38 years). Male patients were 72%. At their planned first postoperative visit, we found no corneal healing abnormalities, such as persistent epithelial defects, epithelial irregularities, or early postoperative stromal haze, in any patient. All patients subjectively reported that proxymetacaine drops helped them to control postoperative pain, particularly in the first 48 h. Conclusions: None of the patients reported pain after 3 days of using proxymetacaine drops up to eight times a day for the first 3 days. It appears to be a safe and effective solution to control postoperative pain without any complications. Full article

Background: Topical statin therapy holds promise for ocular diseases, such as age-related macular degeneration, but the effective delivery to the posterior segment is limited by poor aqueous solubility, chemical instability, and ocular barriers. Cyclodextrins (CDs) can enhance statin solubility and stability; however, the behavior of CD–statin complexes in aqueous eye drops—particularly their influence on the equilibrium between the inactive lactone (ring closed) and active hydroxyacid forms (ring open)—remains unclear. This study aimed to (i) investigate how 5% and 10% (w/v) concentrations of selected CDs affect the lactone/acid equilibrium of simvastatin and atorvastatin and (ii) define formulation parameters (statin form, CD type and concentration, and pH range) for stable eye drop development. Methods: Simvastatin or atorvastatin was added to buffered solutions (pH 2.0 to pH 9.5) of RMβCD, HPβCD, γ-CD, or SBEβCD at 0%, 5%, and 10% (w/v), incubated at 23 ± 1 °C, and sampled over time for UPLC quantification of lactone and hydroxyacid forms, and rate constants for the forward and reverse reaction were calculated. Phase solubility studies were also conducted to further characterize equilibrium behavior in aqueous CD systems. Results: The lactone form was most stable at a pH of 4.5, while the hydroxyacid form prevailed at a pH ≥ 7. γ-CD and HPβCD accelerated lactone hydrolysis for both statins, whereas RMβCD exerted a stabilizing effect. Increasing the CD concentration from 5% to 10% provided minimal additional stabilization. Conclusions: These findings highlight that the precise control of the pH, an appropriate cyclodextrin choice, and the selection of the statin form are critical to developing chemically stable eye drops. Full article

Purpose: To profile tear cytokine changes in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) patients after instillation of daily topical cyclosporine-A 0.1% cationic emulsion. Methods: Participants in a longitudinal study were given cyclosporine eyedrops daily from 3 to 5 weeks before and 3 months, 6 months, and 12 months post-HSCT. The outcomes included tear cytokine concentration assayed by the Proximity Extension Assay O-linked target 96 platform. The patients were divided into two groups: Group 1 (n = 8 conjunctival CD4 cells responding to cyclosporine) and Group 2 (n = 5 conjunctival CD4 cells not suppressed after cyclosporine, where patients were non-compliant with cyclosporine). All participants had a standardized clinical examination, including meibomian gland evaluation and tear breakup times. Results: The levels of 38 cytokines/chemokines showed significant changes (p < 0.05) over time, and in many, the elevation was marked at one year. These include gamma-interferon, CXCL9, CCL3, and CCL4 (all p < 0.0001). For gamma-interferon, there was significant interaction between group and time at 1 year (p = 0.022), where the cytokine was significantly suppressed in Group 1. Four other cytokines showed significant group and time interaction at 1 year: FGF23, FGF5, LIFR, and Enrage (all p < 0.05). All patients had either withdrawal or a reduction in systemic immunomodulation between 6 months and 1 year. We found several cytokines to be associated with changes in tear osmolarity or symptom scores. Conclusions: HSCT induces significant elevation of 38 tear cytokines/chemokines even without the occurrence of ocular graft-versus-host disease when systemic immunosuppression is reduced within the first year. Topical daily cyclosporine eyedrops can reduce some pro-inflammatory tear cytokines. Full article

Background/Objectives: Dry eye disease (DED) is a common condition that can significantly impact cataract surgery outcomes. Preoperative management strategies, including the use of moisturizing eye drops, may improve ocular surface health and postoperative recovery. This study aimed to compare postoperative outcomes in 71 patients undergoing cataract surgery between June 2022 and May 2023 at a single center with and without preoperative keratostill moisturizing eye drops (sterile aqueous 0.3% hydroxypropyl methylcellulose solution) determined using the ocular surface disease index (OSDI), tear break-up time (TBUT), and optical coherence tomography (OCT) at diagnosis, on the day of surgery, and at two weeks postoperatively. Methods: A prospective observational study was conducted on 71 patients undergoing cataract surgery at Saint Barbara Hospital Trauma Center, Sosnowiec, Poland, from June 2022 to May 2023. Patients were randomly assigned to a test group (moisturizing eye drops) or a control group (no preoperative eye drops). The OSDI, TBUT, and OCT were evaluated at the baseline, preoperatively, and postoperatively. Results: The test group showed a significant improvement in OSDI scores (preoperative: 6.34 vs. baseline: 11.81; p < 0.001), which further decreased postoperatively (3.30; p < 0.001). TBUT also significantly increased from baseline to the preoperative visit (6.20 s to 7.97 s; p = 0.002) and remained stable after surgery (7.78 s). In contrast, the control group demonstrated only a minimal postoperative change in OSDI (3.92 to 3.70; p > 0.05) and a significant postoperative decrease in TBUT (5.96 s to 5.69 s; p = 0.864). Only the control group showed a significant postoperative decrease in epithelial thickness in operated eyes (p = 0.021), whereas no significant changes were observed in the test group. Conclusions: The preoperative use of moisturizing eye drops significantly improves the tear film stability, ocular comfort, and epithelial integrity, leading to better postoperative outcomes in cataract surgery patients. Full article

Retinal diseases can result in blindness and visual impairment. They represent a significant medical burden and adversely affect life expectancy. Recently, antibody- and nucleic acid-based pharmaceuticals have increasingly been used to treat retinal diseases, with improvement or cure as the goal; however, these drugs are currently only administered by intravitreal injection. In this study, we present a novel approach to treating retinal diseases using eye drops that contain PnkRNA, a single-stranded RNA nucleic acid. PnkRNA-loaded liposomes were shown to effectively deliver retinal drugs and significantly inhibit retinal thickening in a mouse retinal-vein occlusion model. Cationic modification of the liposome surface enhanced the delivery of nucleic acids and therapeutic efficacy. Moreover, to reduce the frequency of eye-drop administration, liposomes were incorporated into the thermoresponsive gels. This formulation provided sustained retinal delivery and exhibited superior therapeutic efficacy compared with liposomal eye drops. This nucleic acid retinal delivery technology represents a significant advancement in drug-delivery technology, offering a safe and simple treatment for retinal diseases. Full article

Ocular drug delivery presents a persistent clinical challenge due to the protective anatomical structure of the eye, physiological barriers such as reflex blinking, and continuous tear fluid turnover. These factors significantly limit the bioavailability of topically applied medications, reducing the therapeutic effectiveness of conventional formulations, such as eye drops, ointments, and suspensions, particularly in the management of chronic ocular disorders, including dry eye syndrome, diabetic retinopathy, and age-related macular degeneration. Drug-eluting contact lenses (DECLs) offer a promising alternative, enabling sustained, localized, and controlled drug release directly at the ocular surface. While several reviews have addressed contact lenses as drug delivery platforms, this work provides a distinct perspective by focusing specifically on biodegradable polymer-based systems. Emphasis is placed on recent advances in the design and fabrication of DECLs using natural and synthetic biodegradable polymers, which offer superior biocompatibility, customizable degradation kinetics, and the capacity for programmable drug release. This review discusses the selection criteria for polymer matrices, strategies for drug incorporation, and key factors influencing release profiles. Moreover, this study highlights innovative methodologies and therapeutic approaches that differentiate it from the existing literature, providing a timely and comprehensive resource for researchers developing next-generation polymeric ocular drug delivery systems. Full article

Dry eye is an ophthalmic disease with an intricate pathomechanism, and there are no effective interventions or medications available. We investigated the effects of a peptide, DFCPPGFNTK (DFC), screened from tilapia skin hydrolysate on dry eye and its underlying mechanisms. In vitro, human corneal epithelial cells (HCECs) were challenged by 100 mM NaCl in a hyperosmotic environment. DFC restored the cell viability of HCECs induced by NaCl, reduced the transition of mitochondrial membrane potential, delayed the apoptosis of damaged cells, reduced the production of reactive oxygen (ROS) and malondialdehyde (MDA), increased the activities of superoxide dismutase (SOD) and catalase (CAT), and increased the expression rate of Bcl-2/Bax. Compared to the model group, the protein expression levels of COX-2 and iNOS were down-regulated, the mRNA expression of Tnf-α and Il-6 were decreased, the protein expression levels of Nrf2 and HO-1 were increased, and the levels of autophagy-related proteins p62 and LC3B were regulated. In vivo, the dry eye model was developed by administering eye drops of 0.2% BAC to mice for 14 days. DFC increased tear secretion, changed the morphology of tear fern crystals, prevented corneal epithelial thinning, reduced the loss of conjunctival goblet cells (GCs), and inhibited the apoptosis of mice corneal epithelial cells. In summary, DFC improved dry eye by inhibiting oxidative stress, apoptosis, inflammation, and autophagy. Full article